Basic concepts of Radiation Therapy Flashcards
cancer in pet animals
Common, increasing prevalence
Every 2nd dog is euthanized due to „cancer“
Radiation therapy: second most used treatment modality in man
Model for research
resection “en bloc”
can’t remove just the tumour as tumour cells remain in the surrounding tissue
roles of radiation therapy
INCOMPLETELY RESECTED TUMORS (treatment of choice) Non resectable tumors (results depending of tumor type) Pain control (Bone cancer/bone mets)
ionising radiation
Direct damage
Indirect damage (free radicals)
Unit for RT: Grey
reproductive death
DNA damaged - cell dies or lives but is unable to divide further
damage to DNA by ionising radiation effects
Mitosis delayed (10-100Gy)
Radiation damaged cells usually die after 1 or 2
attempts at mitosis
Tissues with high proliferation rate express radiation damage relatively quickly
most radiation sensitive cells
undifferentiated high mitotic rate bone marrow intestinal crypt cells germinal layer of epidermis tumours Tumoral mecanisms of DNA repair not as efficient as in normal cells
fractionation
The total dose of radiation used to treat a tumour is
usually divided into a number of fractions
spares normal tissues because it allows repair of sublethal damage and repopulation
increases damage to tumour because of reoxygenation + redistribution of cells into radiosensitive phases of cell cycle
4 R’s of radiation therapy
repair
repopulation
reoxygenation
redistribution
repair
tumor cells less able to repair DNA damage (Tumor cells are often oxygen + nutrient deficient)
repopulation
RT will often stimulate cell division.
Cells may respond to the death of adjacent cells by “accelerated repopulation”
In normal tissue this is kept under control by normal homeostatic mechanisms, but this is not true for the tumour.
need to give another dose to counteract repopulation + kill the cells
reoxygenation
The tumor contains a mix of aerated and hypoxic cells.
Immediately after RT, most cells in the tumor are hypoxic, but they tend to return at the pre-RT pattern because of reoxygenation
redistribution
Cells are more sensitive to RT in some phases: M-G2-G1-ES-LS
The remaining cells will be “synchronized” + eventually will move into a more sensitive phase
this is when to give next RT fraction
types of radiation used for radiotherapy
X-rays - Orthovoltage, 120-300kVp (not used much), Megavoltage, >1MeV “Linear accelerator”
Gamma rays - Cobalt-60, 1.2MeV
Particles - particles (electrons) in radioisotopes - Strontium-90: plesiotherapy, Iridium-192: brachytherapy
treatment machines
Cobalt-60-therapy unit
Linear accelerator
Cobalt-60-therapy unit
Radioactive source
Photons
Fixed energy (1.24 MV)
Technical requirements ↓
linear accelerator
Variable energies electrons / photons No radioactivity High technical maintenance High accuracy
electron beam
Various energies possible (e.g. 5-16 MeV)
Rapid dose reduction (depending on energy)
Therapeutically useful depth: 1.5-5.6 cm
Single fields, simple dose calculation
photon beam
High penetration Slow dose reduction Field arrangements necessary Penetration of normal tissue CT-based treatment planning
goals of radiation therapy
curative/definitive (long term tumour control)
palliative (palliation, stabilisation of disease, pain reduction)
curative radiation therapy
Absolute Indications - RT shows better results than other therapies
Relative Indications - RT shows same tumor control, but other advantages (functional, cosmetic)
Combination therapy - RT + surgery +/- chemo
primary Tx modality
Brain tumor, tumor of head and neck (oral, nasal), MCT, epulis
post Sx adjuvant RT
Mast cell tumor, Soft tissue sarcoma, Feline vaccine-associated sarcoma, etc.
nasal tumours
2/3 carcinomas; 1/3 sarcomas median survival without treatment ~ 3 months surgery alone ~ 3-6 months radiation therapy alone: ~ 8-20 months RT + SX: 47 months
brain tumours - pituitary tumours
85% of animals show rapid improvement of clinical signs
clinical signs, localization and size could not be shown to have prognostic significance
Very few side effects
oral tumours
acantomatous epulides - 90% tumour control, 86% 3y PFI 4cm
oral scc - 45Gy, 1y PFI 75%
oral fsa - 33-67% 1y PFI
squamous cell carcinoma - dog
Middle aged dogs Rostral mandible Often cauliflower-like Local invasive Metastases - nontonsillar ~ 20%, tonsillar ~70% Prognosis -> site-dependent rostral: local control -> cure tonsillar: < 10% survive 1 year
epulis
no metastases
90% cure rate with curative RT
soft tissue sarcoma - dog
treat - surgery (+/- RT)
chemo
feline injection-site sarcomas
Relationship between VAS and vaccination Incidence unknown 1/1000 – 1/10 000 cats
Tumor volume on contrast-enhanced CT ~ twice the volume measured using calipers on PE
Metastasis in 12-24%
ISS therapy - surgery alone
10% cure rate with surgery alone (high probability of recurrence even with clean margins)
Surgery, conservative: recurrence after 2 months (median)
Surgery, radical: recurrence after 9 months (median)
ISS therapy - surgery + RT
Recurrence: 600 days (median)
40% cure rate
Chemotherapy?
Prognostic factors - no. of surgeries, margins
oral fibrosarcoma
Histologically low-grade but biologically high-grade fsa Golden retriever predisposed Maxilla > mandible V. invasive locally Often intact epithelium Metastasis in ~ 20% (lymph nodes, lungs)
palliative radiation therapy
radiosensitive tumours w/high mets rate - histiocytic sarcoma, oral melanoma, hemangiosarcoma, Mast cell tumor grade III
mass effect - Large head and neck tumors, brain tumors, large sublumbar LN, prostatic tumor, etc
pain control - Osteosarcoma, metastatic bone tumors, etc
malignant melanoma
Most common oral tumor in dogs
Mainly older dogs (mean 11.4 y)
Highly metastatic potential
1/3 amelanotic
RT: Overall response: 83%-94%, Complete response: 53%-69%
Negative prognostic factors - macroscopic disease, bone lysis, caudal location
adverse effects of radiation TX
Some normal cells will die when they try to divide
RT effect may not be apparent until the irradiated cells attempt mitosis
Normal tissue included in radiation field
acute effect - will resolve rapidly dividing tissue: - Tumor, skin, mucosa, GI epithelium
late effect - permanent - Slowly dividing/non-dividing tissue: - Bone, muscle, brain, CNS, lens, retina, etc.
acute side effects
After the third week of radiation 7-10 days post RT → maximum Normal tissue reactions mucous membranes - mucositis skin - alopecia, dermatitis eyes - keratitis / conjunctivitis [CNS - transient demyelination] Self limiting Only symptomatic treatment
acute side effects - skin/dermis
Target cells: stratum basale => erythema, scaly or moist dermatitis, alopecia
Treatment options - Protection from mechanical trauma (collar), Analgesia, no creams/ointments/gels
acute side effects - mucous membranes
Hypersalivation, nasal discharge, mucositis (fibrinous plaques)
Pain - anorexia (rare in dogs, frequent in cats)
Treatment - Pain medication, antibiotics, feeding-tube (PEG) or esophageal tube, Metamucil / lactulose for colitis and proctitis
acute side effects - eyes
Decreased tear production, conjunctivitis, blepharitis, cornea ulceration
Treatment - Optimmune / Vit. A eye ointment, Check tear production
acute side effects - brain/spinal cord
Edema (8-12 weeks post RT)
Transient demyelination - transient „recurrence“ of neurological symptoms
Treatment - Corticosteroids
late side effects
Damage in stroma and vasculature Earliest onset: 6 months after RT Fibroses, contractions, strictures Non healing ulcerations Necrosis (bone, skin, CNS) Cataract, KCS Infarctions, hemorrhagias Therapeutical intervention difficult
late side effects - skin/dermis
Damage of vasculature and fibroblasts
Fibrosis
Alopecia bzw. pigment changes
late side effects - eyes
Cataract (clearing of fibres of lens not possible)
Chronic keratoconjunctivitis sicca
late side effects - brain/spinal cord
Necrosis of white matter (6-18 months)
Vasculopathy (1-4 years)
Differentiation with diagnostic imaging difficult (side effect or recurrent disease?)
Try treatment with corticosteroids
